Liquid chromatography (LC), also termed high performance liquid chromatography (HPLC) or supercritical fluid chromatography (SFC), is a technique used for the separation and quantification of molecules in a liquid. An analyte is injected onto a column filled with separation media and detected post-separation using one or more detectors. Many different types of detectors exist that operate on a variety of detection principles including refractive index (RI), ultraviolet-visible light (UV-VIS), evaporative light-scattering (ELSD), and mass spectrometry (MS) detectors. No single detector is capable of detecting all organic molecules and many have major limitations that restrict their use to certain classes of compounds and/or concentration ranges. For example, UV-VIS detectors are sensitive to molecules that have chromophores and absorb light in certain wavelengths. RI detectors have low sensitivities and are only sensitive to compounds that have refractive indices different from that of the solvent. MS detectors are difficult to use for quantification because of the large effects of solvents and they are highly sensitive to buffers found in LC streams. For these reasons, a variety of detectors are typically employed for robust chemical analysis. A detector that is highly sensitive to a broad range of organic compounds would drastically simplify analysis and reduce the costs of multiple detector schemes.
The flame ionization detector (FID) is a highly sensitive technology capable of detecting the majority of carbon containing compounds with a large linear response. The FID is the most common detector for gas chromatography, but no commercial LC-FID technology exists today because of the difficulties of sample introduction of non-volatile species into the flame. In addition, the large amount of organic solvents in typical LC streams can saturate the FID and lead to low, or negligible, detection.
Several methods for the introduction of samples into FIDs are known and include designs whereby the column effluent is applied to a moving substrate and the mobile phase is evaporated. The analytes are then carried on the moving substrate into a heated zone and volatilized either by boiling, gas-phase oxidation or gas-phase cracking reactions. These designs have included moving belts (Privett, O. S.; Erdahl, W. L., Anal. Biochem. 1978, 84:449), wires (Lapidus, B. M.; Karmen, A., J. Chromatogr. Sci. 1972, 10:103-106), chains (Karmen, A., J. Sep. Sci. 1967, 2:387-397), and rotating discs (Dubsky, H., J. Chromatogr. 1972, 71:395-399; U.S. Pat. No. 3,788,479A). Two commercial versions, which are now discontinued due to issues with sensitivity and reliability, were sold by Pye Unicam Ltd and Tracor Instruments. In addition, several methods have been described for the injection of LC streams directly into the FID using direct column connections (Guillemin, C. L.; Millet, J. L.; Dubois, J., J. High Resolut. Chromatogr. 1981, 4:280; Miller, D. J.; Hawthorne, S. B., Anal. Chem. 1997, 69:623-627) and nebulizers (Young, E.; Smith, R. M.; Sharp, B. L.; Bone, J. R., J. Chrom. A, 2012, 1236:16-20; WO2002018939A2; U.S. Pat. No. 8,920,658B2; U.S. Pat. No. 8,695,813B2; EP2089128A4; EP2089128A1), but these methods are restricted to the small subset of LC users who do not use organic solvents for separation (i.e., super-heated water chromatography or SHWC), they often have low analyte transfer efficiencies and the large amount of water can cause flame instabilities. Improved methods for the introduction of LC effluents to the FID are continually sought.